The Cytotoxic Role of Intermittent High Glucose on Apoptosis and Cell Viability in Pancreatic Beta Cells

Objectives. Glucose fluctuations are both strong predictor of diabetic complications and crucial factor for beta cell damages. Here we investigated the effect of intermittent high glucose (IHG) on both cell apoptosis and proliferation activity in INS-1 cells and the potential mechanisms. Methods. Ce...

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Main Authors: Zhen Zhang, Jing Li, Lei Yang, Rongping Chen, Rui Yang, Hua Zhang, Dehong Cai, Hong Chen
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2014/712781
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author Zhen Zhang
Jing Li
Lei Yang
Rongping Chen
Rui Yang
Hua Zhang
Dehong Cai
Hong Chen
author_facet Zhen Zhang
Jing Li
Lei Yang
Rongping Chen
Rui Yang
Hua Zhang
Dehong Cai
Hong Chen
author_sort Zhen Zhang
collection DOAJ
description Objectives. Glucose fluctuations are both strong predictor of diabetic complications and crucial factor for beta cell damages. Here we investigated the effect of intermittent high glucose (IHG) on both cell apoptosis and proliferation activity in INS-1 cells and the potential mechanisms. Methods. Cells were treated with normal glucose (5.5 mmol/L), constant high glucose (CHG) (25 mmol/L), and IHG (rotation per 24 h in 11.1 or 25 mmol/L) for 7 days. Reactive oxygen species (ROS), xanthine oxidase (XOD) level, apoptosis, cell viability, cell cycle, and expression of cyclinD1, p21, p27, and Skp2 were determined. Results. We found that IHG induced more significant apoptosis than CHG and normal glucose; intracellular ROS and XOD levels were more markedly increased in cells exposed to IHG. Cells treated with IHG showed significant decreased cell viability and increased cell proportion in G0/G1 phase. Cell cycle related proteins such as cyclinD1 and Skp2 were decreased significantly, but expressions of p27 and p21 were increased markedly. Conclusions. This study suggested that IHG plays a more toxic effect including both apoptosis-inducing and antiproliferative effects on INS-1 cells. Excessive activation of cellular stress and regulation of cyclins might be potential mechanism of impairment in INS-1 cells induced by IHG.
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spelling doaj-art-06c0bd88fb3c4e60b33bbea28adce68e2025-08-20T02:02:50ZengWileyJournal of Diabetes Research2314-67452314-67532014-01-01201410.1155/2014/712781712781The Cytotoxic Role of Intermittent High Glucose on Apoptosis and Cell Viability in Pancreatic Beta CellsZhen Zhang0Jing Li1Lei Yang2Rongping Chen3Rui Yang4Hua Zhang5Dehong Cai6Hong Chen7Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaDepartment of Endocrinology, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen 518052, ChinaDepartment of Nephrology, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, ChinaDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaObjectives. Glucose fluctuations are both strong predictor of diabetic complications and crucial factor for beta cell damages. Here we investigated the effect of intermittent high glucose (IHG) on both cell apoptosis and proliferation activity in INS-1 cells and the potential mechanisms. Methods. Cells were treated with normal glucose (5.5 mmol/L), constant high glucose (CHG) (25 mmol/L), and IHG (rotation per 24 h in 11.1 or 25 mmol/L) for 7 days. Reactive oxygen species (ROS), xanthine oxidase (XOD) level, apoptosis, cell viability, cell cycle, and expression of cyclinD1, p21, p27, and Skp2 were determined. Results. We found that IHG induced more significant apoptosis than CHG and normal glucose; intracellular ROS and XOD levels were more markedly increased in cells exposed to IHG. Cells treated with IHG showed significant decreased cell viability and increased cell proportion in G0/G1 phase. Cell cycle related proteins such as cyclinD1 and Skp2 were decreased significantly, but expressions of p27 and p21 were increased markedly. Conclusions. This study suggested that IHG plays a more toxic effect including both apoptosis-inducing and antiproliferative effects on INS-1 cells. Excessive activation of cellular stress and regulation of cyclins might be potential mechanism of impairment in INS-1 cells induced by IHG.http://dx.doi.org/10.1155/2014/712781
spellingShingle Zhen Zhang
Jing Li
Lei Yang
Rongping Chen
Rui Yang
Hua Zhang
Dehong Cai
Hong Chen
The Cytotoxic Role of Intermittent High Glucose on Apoptosis and Cell Viability in Pancreatic Beta Cells
Journal of Diabetes Research
title The Cytotoxic Role of Intermittent High Glucose on Apoptosis and Cell Viability in Pancreatic Beta Cells
title_full The Cytotoxic Role of Intermittent High Glucose on Apoptosis and Cell Viability in Pancreatic Beta Cells
title_fullStr The Cytotoxic Role of Intermittent High Glucose on Apoptosis and Cell Viability in Pancreatic Beta Cells
title_full_unstemmed The Cytotoxic Role of Intermittent High Glucose on Apoptosis and Cell Viability in Pancreatic Beta Cells
title_short The Cytotoxic Role of Intermittent High Glucose on Apoptosis and Cell Viability in Pancreatic Beta Cells
title_sort cytotoxic role of intermittent high glucose on apoptosis and cell viability in pancreatic beta cells
url http://dx.doi.org/10.1155/2014/712781
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